Evaluation of baculoviruses as gene therapy vectors for brain cancer

Autores
Garcia Fallit, Matías; Pidre, Matías Luis; Asad, Antonela S.; Peña Agudelo, Jorge A.; Vera, Mariana B.; Nicola Candia, Alejandro J.; Sagripanti, Sofia B.; Pérez Kuper, Melanie; Amorós Morales, Leslie Cinthya; Marchesini, Abril; Gonzalez, Nazareno; Caruso, Carla M.; Romanowski, Víctor; Seilicovich, Adriana; Videla Richardson, Guillermo A.; Zanetti, Flavia A.; Candolfi, Marianela
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
We aimed to assess the potential of baculoviral vectors (BV) for brain cancer gene therapy. We compared them with adenoviral vectors (AdV), which are used in neuro-oncology, but for which there is pre-existing immunity. We constructed BVs and AdVs encoding fluorescent reporter proteins and evaluated their transduction efficiency in glioma cells and astrocytes. Naïve and glioma-bearing mice were intracranially injected with BVs to assess transduction and neuropathology. Transgene expression was also assessed in the brain of BV-preimmunized mice. While the expression of BVs was weaker than AdVs in murine and human glioma cell lines, BV-mediated transgene expression in patient-derived glioma cells was similar to AdV-mediated transduction and showed strong correlation with clathrin expression, a protein that interacts with the baculovirus glycoprotein GP64, mediating BV endocytosis. BVs efficiently transduced normal and neoplastic astrocytes in vivo, without apparent neurotoxicity. BV-mediated transgene expression was stable for at least 21 days in the brain of naïve mice, but it was significantly reduced after 7 days in mice systemically preimmunized with BVs. Our findings indicate that BVs efficiently transduce glioma cells and astrocytes without apparent neurotoxicity. Since humans do not present pre-existing immunity against BVs, these vectors may constitute a valuable tool for the delivery of therapeutic genes into the brain.
Instituto de Biotecnología y Biología Molecular
Materia
Biología
Ciencias Médicas
Baculoviruses
Glioblastoma
Astrocytes
Gene therapy
Brain
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/152929

id SEDICI_4b1289208e7b7653d2b0130812bfd067
oai_identifier_str oai:sedici.unlp.edu.ar:10915/152929
network_acronym_str SEDICI
repository_id_str 1329
network_name_str SEDICI (UNLP)
spelling Evaluation of baculoviruses as gene therapy vectors for brain cancerGarcia Fallit, MatíasPidre, Matías LuisAsad, Antonela S.Peña Agudelo, Jorge A.Vera, Mariana B.Nicola Candia, Alejandro J.Sagripanti, Sofia B.Pérez Kuper, MelanieAmorós Morales, Leslie CinthyaMarchesini, AbrilGonzalez, NazarenoCaruso, Carla M.Romanowski, VíctorSeilicovich, AdrianaVidela Richardson, Guillermo A.Zanetti, Flavia A.Candolfi, MarianelaBiologíaCiencias MédicasBaculovirusesGlioblastomaAstrocytesGene therapyBrainWe aimed to assess the potential of baculoviral vectors (BV) for brain cancer gene therapy. We compared them with adenoviral vectors (AdV), which are used in neuro-oncology, but for which there is pre-existing immunity. We constructed BVs and AdVs encoding fluorescent reporter proteins and evaluated their transduction efficiency in glioma cells and astrocytes. Naïve and glioma-bearing mice were intracranially injected with BVs to assess transduction and neuropathology. Transgene expression was also assessed in the brain of BV-preimmunized mice. While the expression of BVs was weaker than AdVs in murine and human glioma cell lines, BV-mediated transgene expression in patient-derived glioma cells was similar to AdV-mediated transduction and showed strong correlation with clathrin expression, a protein that interacts with the baculovirus glycoprotein GP64, mediating BV endocytosis. BVs efficiently transduced normal and neoplastic astrocytes in vivo, without apparent neurotoxicity. BV-mediated transgene expression was stable for at least 21 days in the brain of naïve mice, but it was significantly reduced after 7 days in mice systemically preimmunized with BVs. Our findings indicate that BVs efficiently transduce glioma cells and astrocytes without apparent neurotoxicity. Since humans do not present pre-existing immunity against BVs, these vectors may constitute a valuable tool for the delivery of therapeutic genes into the brain.Instituto de Biotecnología y Biología Molecular2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://sedici.unlp.edu.ar/handle/10915/152929enginfo:eu-repo/semantics/altIdentifier/issn/1999-4915info:eu-repo/semantics/altIdentifier/doi/10.3390/v15030608info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/Creative Commons Attribution 4.0 International (CC BY 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-09-29T11:39:33Zoai:sedici.unlp.edu.ar:10915/152929Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-29 11:39:33.575SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv Evaluation of baculoviruses as gene therapy vectors for brain cancer
title Evaluation of baculoviruses as gene therapy vectors for brain cancer
spellingShingle Evaluation of baculoviruses as gene therapy vectors for brain cancer
Garcia Fallit, Matías
Biología
Ciencias Médicas
Baculoviruses
Glioblastoma
Astrocytes
Gene therapy
Brain
title_short Evaluation of baculoviruses as gene therapy vectors for brain cancer
title_full Evaluation of baculoviruses as gene therapy vectors for brain cancer
title_fullStr Evaluation of baculoviruses as gene therapy vectors for brain cancer
title_full_unstemmed Evaluation of baculoviruses as gene therapy vectors for brain cancer
title_sort Evaluation of baculoviruses as gene therapy vectors for brain cancer
dc.creator.none.fl_str_mv Garcia Fallit, Matías
Pidre, Matías Luis
Asad, Antonela S.
Peña Agudelo, Jorge A.
Vera, Mariana B.
Nicola Candia, Alejandro J.
Sagripanti, Sofia B.
Pérez Kuper, Melanie
Amorós Morales, Leslie Cinthya
Marchesini, Abril
Gonzalez, Nazareno
Caruso, Carla M.
Romanowski, Víctor
Seilicovich, Adriana
Videla Richardson, Guillermo A.
Zanetti, Flavia A.
Candolfi, Marianela
author Garcia Fallit, Matías
author_facet Garcia Fallit, Matías
Pidre, Matías Luis
Asad, Antonela S.
Peña Agudelo, Jorge A.
Vera, Mariana B.
Nicola Candia, Alejandro J.
Sagripanti, Sofia B.
Pérez Kuper, Melanie
Amorós Morales, Leslie Cinthya
Marchesini, Abril
Gonzalez, Nazareno
Caruso, Carla M.
Romanowski, Víctor
Seilicovich, Adriana
Videla Richardson, Guillermo A.
Zanetti, Flavia A.
Candolfi, Marianela
author_role author
author2 Pidre, Matías Luis
Asad, Antonela S.
Peña Agudelo, Jorge A.
Vera, Mariana B.
Nicola Candia, Alejandro J.
Sagripanti, Sofia B.
Pérez Kuper, Melanie
Amorós Morales, Leslie Cinthya
Marchesini, Abril
Gonzalez, Nazareno
Caruso, Carla M.
Romanowski, Víctor
Seilicovich, Adriana
Videla Richardson, Guillermo A.
Zanetti, Flavia A.
Candolfi, Marianela
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Biología
Ciencias Médicas
Baculoviruses
Glioblastoma
Astrocytes
Gene therapy
Brain
topic Biología
Ciencias Médicas
Baculoviruses
Glioblastoma
Astrocytes
Gene therapy
Brain
dc.description.none.fl_txt_mv We aimed to assess the potential of baculoviral vectors (BV) for brain cancer gene therapy. We compared them with adenoviral vectors (AdV), which are used in neuro-oncology, but for which there is pre-existing immunity. We constructed BVs and AdVs encoding fluorescent reporter proteins and evaluated their transduction efficiency in glioma cells and astrocytes. Naïve and glioma-bearing mice were intracranially injected with BVs to assess transduction and neuropathology. Transgene expression was also assessed in the brain of BV-preimmunized mice. While the expression of BVs was weaker than AdVs in murine and human glioma cell lines, BV-mediated transgene expression in patient-derived glioma cells was similar to AdV-mediated transduction and showed strong correlation with clathrin expression, a protein that interacts with the baculovirus glycoprotein GP64, mediating BV endocytosis. BVs efficiently transduced normal and neoplastic astrocytes in vivo, without apparent neurotoxicity. BV-mediated transgene expression was stable for at least 21 days in the brain of naïve mice, but it was significantly reduced after 7 days in mice systemically preimmunized with BVs. Our findings indicate that BVs efficiently transduce glioma cells and astrocytes without apparent neurotoxicity. Since humans do not present pre-existing immunity against BVs, these vectors may constitute a valuable tool for the delivery of therapeutic genes into the brain.
Instituto de Biotecnología y Biología Molecular
description We aimed to assess the potential of baculoviral vectors (BV) for brain cancer gene therapy. We compared them with adenoviral vectors (AdV), which are used in neuro-oncology, but for which there is pre-existing immunity. We constructed BVs and AdVs encoding fluorescent reporter proteins and evaluated their transduction efficiency in glioma cells and astrocytes. Naïve and glioma-bearing mice were intracranially injected with BVs to assess transduction and neuropathology. Transgene expression was also assessed in the brain of BV-preimmunized mice. While the expression of BVs was weaker than AdVs in murine and human glioma cell lines, BV-mediated transgene expression in patient-derived glioma cells was similar to AdV-mediated transduction and showed strong correlation with clathrin expression, a protein that interacts with the baculovirus glycoprotein GP64, mediating BV endocytosis. BVs efficiently transduced normal and neoplastic astrocytes in vivo, without apparent neurotoxicity. BV-mediated transgene expression was stable for at least 21 days in the brain of naïve mice, but it was significantly reduced after 7 days in mice systemically preimmunized with BVs. Our findings indicate that BVs efficiently transduce glioma cells and astrocytes without apparent neurotoxicity. Since humans do not present pre-existing immunity against BVs, these vectors may constitute a valuable tool for the delivery of therapeutic genes into the brain.
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Articulo
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://sedici.unlp.edu.ar/handle/10915/152929
url http://sedici.unlp.edu.ar/handle/10915/152929
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/issn/1999-4915
info:eu-repo/semantics/altIdentifier/doi/10.3390/v15030608
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International (CC BY 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International (CC BY 4.0)
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:SEDICI (UNLP)
instname:Universidad Nacional de La Plata
instacron:UNLP
reponame_str SEDICI (UNLP)
collection SEDICI (UNLP)
instname_str Universidad Nacional de La Plata
instacron_str UNLP
institution UNLP
repository.name.fl_str_mv SEDICI (UNLP) - Universidad Nacional de La Plata
repository.mail.fl_str_mv alira@sedici.unlp.edu.ar
_version_ 1844616269356072960
score 13.069144